ClinVar Miner

Submissions for variant NM_024301.5(FKRP):c.899T>C (p.Val300Ala) (rs104894691)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000004453 SCV000796383 likely pathogenic Limb-girdle muscular dystrophy-dystroglycanopathy, type C5 2017-12-12 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000732974 SCV000860976 likely pathogenic not provided 2018-05-11 criteria provided, single submitter clinical testing
Invitae RCV000814162 SCV000954563 pathogenic Walker-Warburg congenital muscular dystrophy 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 300 of the FKRP protein (p.Val300Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed to be homozygous or in combination with another FKRP variant in several individuals affected with limb-girdle muscular dystrophy (PMID: 14647208, 15060126, 24447024). ClinVar contains an entry for this variant (Variation ID: 4232). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the p.Val300 amino acid residue in FKRP have been observed in affected individuals (PMID: 14647208, 27848944, Invitae). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000732974 SCV001250134 pathogenic not provided 2019-03-01 criteria provided, single submitter clinical testing
OMIM RCV000004453 SCV000024626 pathogenic Limb-girdle muscular dystrophy-dystroglycanopathy, type C5 2003-12-01 no assertion criteria provided literature only

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