ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2213G>C (p.Ser738Thr) (rs730880894)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497292 SCV000208773 likely pathogenic not provided 2017-03-02 criteria provided, single submitter clinical testing This variant is denoted p.Ser738Thr (S738T) at the protein level and c.2213 G>C at the cDNA level. The Ser738Thr variant in the MYH7 gene has not been reported previously as a disease-causing variant, nor is it known to be a benign polymorphism to our knowledge. Although Ser738Thr results in a conservative amino acid substitution of one polar residue for another, the Serine738 residue is highly conserved throughout evolution. Several pathogenic variants in nearby codons (Ile736Leu, Ile736Met, Ile736Thr, Gly741Ala, Gly741Arg, Gly741Trp) have been reported in association with HCM, supporting the functional importance of this region of the protein. Nevertheless, some but not all in silico algorithms predict Ser738Thr to have a deleterious effect on protein structure/function. In summary, with the clinical and molecular information available at this time, we cannot determine with certainty if Ser738Thr is a disease-causing variant or rare benign variant.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000158838 SCV000280317 uncertain significance not specified 2013-10-16 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Ser738Thr in MYH7 This variant is novel. This is a conservative amino acid substitution of a polar Serine with a polar Threonine. Serine is highly conserved at this position and some in silico algorithms predict the amino acid change to be deleterious to the structure/function of the resulting beta myosin protein. Several nearby variants have been reported in association with cardiomyopathy (p.Ile736Leu, p.Ile736Met, p.Ile736Thr, p.Gly741Ala) in nearby codons. The variant is not listed in dbSNP, 1000 Genomes or NHLBI’s Human Exome Variant Database, which includes MYH7 variant data on ~5,350 individuals of Caucasian and African American ancestry (as of December 2011).

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