ClinVar Miner

Submissions for variant NM_000364.4(TNNT2):c.97G>A (p.Glu33Lys) (rs377474357)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000036314 SCV000059966 uncertain significance not specified 2012-01-10 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Pathogenic. The Glu33Lys va riant (TNNT2) has not been reported in the literature, but has been identified i n 1/7020 European American chromosomes from a broad, though clinically unspecifi ed population (NHLBI Exome Sequencing Project; http://evs.gs.washington.edu/EVS) . This variant has not been previously identified in >3250 probands (>2000 Cauca sian) tested by our laboratory. This low frequency could support a pathogenic ro le. Glutamic acid (Glu) at position 33 is not conserved in mammals or chicken, i ncreasing the likelihood that a change would be tolerated. Computational tools ( AlignGVGD, SIFT) predict that a change to lysine (Lys) would not impact the prot ein. However, this variant occurs at the last base of the exon and this position has been shown to be part of the splicing consensus sequence. Splicing predicti on tools suggest that splicing may be altered. Note, the accuracy of the computa tional and splicing tools is unknown. Collectively, this data suggests that the Glu33Lys variant may be pathogenic, but since it has not been seen in isolation, additional studies are needed to further assess its clinical significance.

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